Solution of arsenobenzene derivatives



, than that of the original arseno compound,

Patented Dec. 7. 192.

UNITED STATES PATENT OFFICE.

GEORGE 'W. BAIZISS AND ABRAHAM KREMENS, OF PHILADELPHIA, PENNSYLVANIA, ASSIGNOBS TO ABBOTT LABORATORIES, OF pHICAGO, ILLINOIS, A CORPORATION OF ILLINOIS.

SOLUTION 0F AIRSENOBENZENE DERIVATIVES.

No Drawing.

- a I I I Li I 0 V The pr ncipal ObJGClJ Of our invention 18 to produce solutions of arsenobenzene derivatives. containing the characteristic group AszAs. for example, arsphenamine, WhlCl shall be stable over long periods, the toxicity of which solution is reduced to a minimum, while the therapeutic efliciency ot'the same is preserved. Such solutions have their chief value in the treatment of syphilis.

Attempts to prepare such stable solutions resulted previously in the lowering not only of the toxicity but also of the therapeutic efiiciency. It has been claimed that simple sugars such as various hexoses: glucose, levulose. mannose, etc. are capable of preventing pxidation of the arseno group. While this finding is true, and the purpose of hindering the oxidation has been accomplished in this way and products were obtained, which are not only stable but also less toxic than the original arseno compound, the possibility has been overlooked that the therapeutic efficiency would be interfered with because of the formation of condensation products in these solutions due to the interaction 0t arsenobenzene compounds with the aldehyde 7 group present in simple sugars. We believe that actual chemical combination takes place with the resulting formation of products of glucosi'de nature.

Should glucosides of arsenobenzene compounds be formed, the therapeutic eficiency of such products will be materially diminished.

For the purpose of preserving the full therapeutic power of the arseno compound used for makin solutions, while stabilizing the same, We ave discovered that disaccharides such aslordinary cane sugar, lactose and maltose, which due to their chemical constitution have not the free aldehyde group for combining with the amino groups or other available groups can diminish the toxicity as well as preserve the arseno com: pounds from oxidation, although without possibly entering into as firm chemical union as the more active hexoses.

With the use of disaccharides, we are able to prepare stable solutions which are not oxidized when kept in sealed ampoules. The toxicity of such solutions is materially lower Application filed July 16, 1924. Serial No. 726,277.

toxicity, enables much larger doses to be safely employed.

We have also found that only moderate concentrations of such disaccharides are necessary for above purposes, satisfactory results having been obtained with solutions containing from 10 to 25% of the disaccharide. These solutions contain the, arseno compound in'concentrations ranging from 5 to 9%.

For arseno compounds such as arsphenajected intravenously just before or after the int-ravenous injections of arsenobenzene derivatives, has a detoxicating influence wlthout interferring with the therapeutic efi'iciency. l? or this reason, we employ as a second detoxicating ingredient sodium thiosulfate in moderate quantities which acts also as a stabilizing agent.

In making such stable solutions ofarsenobenzenes particularly of arsphenamine and itsv derivatives, we prepare a neutral or slightly alkaline solution of the arseno derivative in sterile distilled water in concern tration ranging from 5 to 9%. In this ster- 'ile distilled water, we have previously dissolved a quantity of the disaecharide, for

example, lactose, so as to obtain a solution containin from 5 to 25% of disaccharide. We also issolve in the same solution chemically pure sodium thiosulfatc m the amount 20 ed claims, said claims being construed as of 0.1 to 0.3 gram per ampoule (each ampoulc contains one therapeutic dose of arsenobenzene compound varying from 0.2 am up to a maximum of 0.9 gram). en such solution containing the arsenobenzene derivative, disaccharide, and sodium thiosulfate, is obtained, it is introduced into glass ampoules, which are then attached to .a high-vacuum system for the purpose of removing oxygen. then sealed by means ofa hot ame with such precautions that no air enters the glass container. and ready for intravenous injection without further manipulation by the physician.

The described details being merely illustrative of my invention, it will be under stood that the scope of the invention should be determined by reference to theappend- The am oules are Such solutions are stable as stabilizing and detoxicating ingredients. I

2. As a new article of manufacture, a therapeutic solutlon of an arsenobenzenc derivative, contalning a disaccharide and SOdlum thiosulfate as stabilizing and detoxicab ing ingredients.

3. As a.- new article of manufacture, a solution or arsenobenzene derivative. con taining sodium thiosulfate as a stabilizing 'and detoxicating ingredient.

GEORGE W. RAIZISS. ABRAHAM KREMENS. 

